Background: Intracerebral hemorrhage (ICH) remains a devastating disease and current treatment options lag far behind those for ischemic stroke. Functional outcomes in ICH remain dismal with only 20% of victims being independent at 6 months [1]. To date, there are no approved therapies which improve outcome and treatment remains mainly supportive. Current treatment efforts for ICH are targeted towards the primary brain injury caused by the hemorrhage and growth of the hematoma. This research targets the secondary injury caused by the persistence of toxic blood degradation products in the brain parenchyma. Based on preclinical work in our lab, the peroxisome proliferator activated receptor-gamma (PPARv), a member of the nuclear receptor superfamily, represents a possible target for the treatment of ICH aimed at promoting hematoma absorption, limiting the pro-inflammatory response, and protecting salvageable tissue from the damage produced by the persistence of toxic blood degradation products. Objectives: Our primary specific aim is to assess the safety of the PPARy agonist, pioglitazone (PIO) in increasing doses from 0.1 to 2 mg/kg/d for 3 days, when administered to patients with ICH within 24 hrs of symptom onset. Secondarily, we aim to explore the duration of treatment of PIO for hematoma/edema resolution in ICH. Lastly, we aim to explore whether speed of hematoma/edema resolution in ICH represents a radiographic biological marker of activity which can be correlated with clinical outcome and treatment effect of PIO. The ultimate purpose is to provide baseline data on an aspect of ICH which has not been previously targeted for treatment in an effort to develop a safe and effective treatment strategy that may be practical and applicable for both specialized stroke centers and community hospitals. Study Design and Methods: Prospective, randomized, blinded, placebo-controlled, dose-escalation safety trial in which patients with spontaneous ICH will be randomly allocated to placebo or treatment with escalating doses of short-term high-dose PIO (0.1 to 2.0 mg/kg/d for 3 days) followed by a lower maintenance dose for the duration of treatment. The Continual Reassessment Method for dose-finding will be used to determine the maximum tolerated dose of PIO. Treatment duration will be determined by exploring the time it takes for 75% of the hematoma to resolve. Hematoma and edema resolution will be evaluated with serial MR I at specified time points. Functional outcome will be evaluated at 3 and 6 months with the NIHSS score, Modified Rankin Scale, Barthel Index, and Stroke Impact Scale-16. ICH is a devastating disease with less than 20% of survivors being independent at 6 months. There is currently no approved treatment for ICH which has been shown to improve outcomes. In an effort to develop a new treatment for ICH, this research focuses on a different aspect of ICH treatment which has not yet been evaluated: enhancing absorption of the blood clot with medication. Description from Appendix section: PURPOSE: Intracerebral hemorrhage (ICH) is a type of stroke caused by bleeding into the brain due to a ruptured blood vessel. When a person develops ICH, a part of the brain does not get the oxygen and substances necessary to survive. To date, there are no approved therapies for this condition. The standard of care for ICH is to stop the growth of the blood clot and to control the brain swelling that happens after the injury. Therapies for ICH include medications to aggressively control blood pressure, other medications designed specifically to decrease the rate of bleeding, and surgery in the appropriate patients. Despite these efforts, there has been no treatment which has been shown to improve outcome. Even with these treatments, only 20% of patients with ICH are able to function independently at 6 months. Much research remains to be done in this area. Research in the laboratory and in animal studies shows that a group of medications called "Thiazolidinediones" (TZDs) has been shown to play a positive role in controlling the brain's response to injury. Studies evaluating TZDs in animal models of stroke have found a protective benefit. One of the medications in this class is called pioglitazone (PIO). PIO is currently approved by the Food and Drug Administration for the treatment of type II diabetes in adults. Our research is an investigational, off-label use of this medication in patients with ICH. The purpose of this study is to evaluate the safety of a possible new treatment for ICH. In this study we plan to: [unreadable] Test the safety of PIO, [unreadable] Test how well patients tolerate PIO, [unreadable] Determine how PIO works when used with standard of care treatment in patients